Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response
0
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Purpose The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. Materials and Methods In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. Results Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune-modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.
Abstract
Purpose The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. Materials and Methods In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. Results Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune-modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Conclusion Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.
참고문헌 (29)
- Razumilava N, "Cholangiocarcinoma", Lancet, 383, pp.2168~2179 (2014)
- Siegel RL, "Cancer statistics, 2018", CA Cancer J Clin, 68, pp.7~30 (2018)
- Patel T, "Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States", Hepatology, 33, pp.1353~1357 (2001)
- Edge SB, "The American Joint Committee on Cancer : the 7th edition of the AJCC cancer staging manual and the future of TNM", Ann Surg Oncol, 17, pp.1471~1474 (2010)
- Lamarca A, "ABC-06 | A randomised phase III, multi-centre, openlabel study of active symptom control (ASC) alone or ASC with oxaliplatin", 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced, gemcitabine (CisGem) chemotherapy, pp.J Clinl Oncol, 2019[DOI]
- Valle J, "Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer", N Engl J Med, 362, pp.1273~1281 (2010)
- Valle JW, "Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up", Ann Oncol., 27(Suppl 5), pp.v28~v37 (2016)
- 형재원, "Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin", Cancer Research and Treatment, 51(3), pp.901~909 (2019), 대한암학회
- Kim BJ, "Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin : retrospective analysis of 740 patients", Cancer Chemother Pharmacol, 80, pp.209~215 (2017)
- Eggermont AM, "Adjuvant pembrolizumab versus placebo in resected stage III melanoma", N Engl J Med, 378, pp.1789~1801 (2018)
- Bellmunt J, "Pembrolizumab as second-line therapy for advanced urothelial carcinoma", N Engl J Med, 376, pp.1015~1026 (2017)
- Muro K, "Pembrolizumab for patients with PD-L1-positive advanced gastric cancer(KEYNOTE-012) : a multicentre, openlabel, phase 1b trial", Lancet Oncol, 17, pp.717~726 (2016)
- Garon EB, "Pembrolizumab for the treatment of non-small-cell lung cancer", N Engl J Med, 372, pp.2018~2028 (2015)
- Herbst RS, "Predictive correlates of response to the anti-PD-L1antibody MPDL3280A in cancer patients", Nature, 515, pp.563~567 (2014)
- Topalian SL, "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer", N Engl J Med, 366, pp.2443~2454 (2012)
- Le DT, "Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade", Science, 357, pp.409~413 (2017)
- Le DT, "PD-1 blockade in tumors with mismatch-repair deficiency", N Engl J Med, 372, pp.2509~2520 (2015)
- Silva VW, "Biliary carcinomas : pathology and the role of DNA mismatch repair deficiency", Chin Clin Oncol, 5, pp.62~ (2016)
- Salem ME, "Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers", Mol Cancer Res, 16, pp.805~812 (2018)
- Goeppert B, "Mismatch repair deficiency is a rare but putative therapeutically relevant finding in non-liver fluke associated cholangiocarcinoma", Br J Cancer, 120, pp.109~114 (2019)
- Fontugne J, "PD-L1 expression in perihilar and intrahepatic cholangiocarcinoma", Oncotarget, 8, pp.24644~24651 (2017)
- Bang YJ, "Pembrolizumab(pembro)for advanced biliary adenocarcinoma : results from the KEYNOTE-028(KN028)and KEYNOTE-158(KN158)basket studies", J Clin Oncol, 37(15 Suppl), pp.4079~ (2019)
- Scheel AH, "Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas", Mod Pathol, 29, pp.1165~1172 (2016)
- Dolled-Filhart M, "Development of a companion diagnostic for pembrolizumab in non-small cell lung cancer using immunohistochemistry for programmed death ligand-1", Arch Pathol Lab Med, 140, pp.1243~1249 (2016)
- Kulangara K, "Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer", Arch Pathol Lab Med, 143, pp.330~337 (2019)
- Ueno M, "Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer : a non-randomised, multicentre, openlabel, phase 1 study", Lancet Gastroenterol Hepatol, 4, pp.611~621 (2019)
- Dudley JC, "Microsatellite instability as a biomarker for PD-1 blockade", Clin Cancer Res, 22, pp.813~820 (2016)
- Luchini C, "ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1", PD-L1 expression and tumour mutational burden : a systematic review-based approach, 2019, pp.30, 1232~1243
- Kim BJ, "Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin : retrospective analysis of 321 patients", Br J Cancer, 116, pp.561~567 (2017)